Cholesterol Medications - Medications For Heart Disease: Heart Disease

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Cholesterol medications

Since statins were first introduced in the late 1980s, they have become the treatment of choice for lowering cholesterol, simply because they are so effective. Even so, they don't work for everyone; other medications are available to lower cholesterol and may be more beneficial for you, depending on your circumstances. If you have high triglycerides in addition to high LDL, for instance, the class of drugs known as fibric acid derivatives may help (see "Fibric acid derivatives"). If you have low HDL cholesterol, niacin is an option. Other medications such as colesevelam (WelChol) and ezetimibe (Zetia) lower LDL substantially and can be combined with statins to lower these levels even further (see "A cholesterol-lowering combination").

Statins

Statins, known medically as HMG-CoA reductase inhibitors, work by preventing the liver from making cholesterol (see Figure 7) and by forcing the liver to draw LDL cholesterol from the blood. These medications not only significantly lower LDL levels but also improve your overall cholesterol profile by lowering total cholesterol, slightly boosting HDL, and slightly lowering triglycerides — although by differing amounts. Since they were introduced in 1987, the statins have proved to be better at reducing cholesterol than other medications. What's more, studies have revealed that these medications have other benefits: They stabilize cholesterol-filled plaque in artery walls, promote the growth of new blood vessels, and calm inflammation. All of these actions help to reduce the risk for coronary artery disease and heart attack or stroke. Small wonder that statins are considered one of the most important advances in drug therapy since the 1970s.

Figure 7: How statins work Most of the cholesterol circulating in your blood has been made by your liver, not digested from the food you eat. An enzyme called HMG-CoA reductase plays a key role in deciding how much cholesterol the liver makes.

But statins are not miracle pills, and they're not for everyone. They don't always lower cholesterol enough, and they cause troubling side effects in some people. It's also important to remember that eating healthy foods, exercising regularly, and losing weight if necessary are the best — and should be the first — approaches to treating high cholesterol and reducing the risk for heart attack or stroke. Consider the options carefully and talk with your doctor about whether to take a statin and, if so, which one to take.

Should you take a statin? It depends on a number of factors. In general, the higher your LDL cholesterol, and the greater your chances of having a heart attack or stroke, the more you'd benefit from taking a statin. Talk with your doctor about these drugs if you

• have had a heart attack or get chest pain

• have had coronary artery bypass surgery or artery-opening angioplasty

• have heart disease, diabetes, chronic kidney disease, or vascular disease and your LDL is above 100 mg/dL

• have high LDL (above 160 mg/dL) despite lifestyle changes

• are at high risk of developing heart disease (even though your cholesterol is in the normal range) because of smoking, high blood pressure, a family history of early heart disease, or other factors.

Six statins are now available in the United States: atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin (Zocor). Another medication, Vytorin, combines ezetimibe and simvastatin in a single pill (see "A cholesterol-lowering combination"). All six statins have similar effects on cholesterol and similar side effects. For most people, which statin you take isn't nearly as important as whether you take it every day, how you take it (see "Getting the most from your statin," below), and how well you help it along with diet and exercise (see "Lifestyle changes to protect yourself"). And it's important to remember that although the PROVE IT study (see "The lower the cholesterol, the better") is sometimes depicted as the "clash of the statins," the real message for people at risk for heart disease was to drive LDL levels as low as possible. With all that in mind, here's a quick guide for differentiating among the statins.

Potency. Some statins are more potent than others, in that the same dose of a medication lowers cholesterol by different amounts. A 20-mg tablet of Pravachol, for example, lowers LDL by 24% on average, while a 20-mg tablet of Lipitor lowers it by 46%. But potency isn't nearly as important as efficacy — the maximum amount a statin can lower LDL at its highest FDA-approved dose. Lipitor and Crestor rank highest in this regard. But here's the rub: You don't necessarily need to pick the strongest statin. A "weaker" one may be less expensive and more than enough to get you to your target.

Cost. Statin tablets can cost anywhere between $500 and $1,500 per year. How much you actually pay can depend on the deals your health insurer has made.

Side effects. This issue can be a deciding factor for some people trying to choose among the statins. All six statins can increase levels of liver proteins — a change that affects 2 out of 100 people — although it is not clear if this represents a real problem. Liver failure, a serious problem, is extremely rare in people using statins.

Muscle pain is more problematic. About 5 of every 100 people who take a statin report having muscle pain, but it is not clear whether this is caused by statin use. In large clinical trials, muscle pain was reported by as many people taking a placebo as it was by those taking a statin. (The aches and pains of growing older may be to blame.) Still, some people have muscle aches right after starting a statin that disappear when they stop taking the medication. Severe muscle damage — a condition known as rhabdomyolysis, which can be deadly unless treated — affects about 8 of every 10,000 people taking a statin. One popular statin, cerivastatin (Baycol), was voluntarily removed from the market in 2001 because it was associated with rhabdomyolysis. Crestor came under fire in 2004 when critics charged that it was more likely than other statins to cause rhabdomyolysis and kidney failure. After reviewing the data, however, the FDA issued a public advisory concluding that Crestor was as safe as the other statins in most cases, but warning that to reduce risk, the lowest doses should be prescribed in people older than 65, those who have hypothyroidism or kidney disease, and Asian Americans.

If you take a statin in combination with a fibrate drug such as gemfibrozil (Lopid) or fenofibrate (TriCor), you and your doctor should be especially alert to symptoms of persistent muscle aches and pains, which could indicate rhabdomyolysis. A blood test for creatine kinase, a protein released by injured muscle, can reveal whether damage has occurred.

Because various statins are broken down in the liver in different ways, some statins are more likely to be affected by other drugs or foods. Grapefruit juice, for example, increases blood levels of Mevacor, Zocor, and Lipitor, but doesn't usually affect the other statins. Your doctor may suggest a particular statin based on other medications you are taking.

Finally, all medications affect different people in different ways. Some people taking statins have experienced constipation, upset stomach, dizziness, insomnia, rashes, and even hair loss. Because these could be reactions to either the active agent or the inactive ingredients, changing to a different statin may help. If not, try another cholesterol-lowering drug.

Fibric acid derivatives

This family of drugs blocks the production and activity of proteins that transport cholesterol. The two most commonly prescribed fibric acid derivatives are gemfibrozil (Lopid) and fenofibrate (TriCor). Others are under investigation. Fibric acid derivatives are mainly prescribed for people with high triglyceride levels. They reduce triglycerides by 20%–50% and raise HDL levels by 10%–15%, but have only a modest effect on LDL.

Gemfibrozil and fenofibrate, which come in pill form, are generally taken once or twice a day with meals. Most people don't experience side effects, although a few develop dyspepsia (feelings of fullness, bloating, or heartburn after eating), dizziness, or changes in sensations such as touch and taste. These drugs can also increase the risk for gallbladder disease and, when used with a statin, can cause rare cases of the muscle-wasting disease rhabdomyolysis. They can also augment the effects of blood-thinning drugs such as warfarin.

Although these side effects are uncommon, everyone taking a fibric acid derivative should have checks of liver function and blood counts before and during therapy. And people on blood-thinning medications should have their prothrombin time (a measure of clotting ability) monitored closely.

Niacin

The B vitamin niacin, also called nicotinic acid, is an essential part of a healthy diet. At daily doses of 1,500–4,500 mg — well above the Recommended Dietary Allowance (14 mg for women and 16 mg for men) — crystalline nicotinic acid acts as a drug instead of a vitamin. Niacin alone can reduce LDL levels by 15% or so, lower triglycerides even more, and boost HDL by as much as 20%. Taken in addition to a statin, niacin lowers LDL another 10%. It works by cutting the liver's production of VLDL, which is ordinarily converted into LDL.

Although you can buy niacin in any grocery or health store, to obtain the necessary dose, it's best to go with a preparation approved by the FDA (see Table 11). Niacin is safe, except for people with chronic liver disease or certain other conditions, including diabetes and peptic ulcer. It's also inexpensive. However, it has numerous side effects. It can cause rashes and may aggravate gout, diabetes, or peptic ulcers. A sustained-release preparation (Niaspan) may have fewer side effects, but it can cause liver damage, especially when combined with a statin.

Bile acid binders

Bile acid binders are synthetic resins that bind chemically with cholesterol-rich bile acids in the intestine, preventing their reabsorption. To replace the bile acids lost in this way, the body draws upon its store of cholesterol, thus lowering cholesterol levels in the blood. Medications in this class include cholestyramine (Questran), colesevelam (WelChol), and colestipol (Colestid). Typically, they lower LDL cholesterol by 15%–30%, depending on the daily dose and whether they are combined with a statin.

But bile acid binders are rarely used, because of their many side effects. These include constipation, heartburn, and a bloated feeling. The soluble fiber psyllium, found in laxatives such as Metamucil, Perdiem, and others, can lessen these side effects. However, bile acid binders can also interfere with the action of many drugs, especially digitalis, beta blockers, warfarin, thiazide diuretics, anticonvulsants, and thyroid hormone supplements. And people with high triglyceride levels should not take this type of medication because it tends to elevate triglycerides.

Ezetimibe (Zetia)

If you are one of the people who has not been helped at all by statins, it may be because your genes and biology make you resistant to the drugs' effects. In 2002 the FDA approved a medication that has proved to be the most helpful in people who least benefited from statin treatment.

Zetia works by blocking the cholesterol in food from crossing the intestinal wall and getting into the bloodstream. Using a mathematical model, researchers at the Florida Lipid Institute showed that people whose LDL budged little with a statin had higher than expected drops in LDL after adding Zetia. This seesaw connection between the statins and Zetia makes some sense, because people for whom statins don't work well are great at absorbing cholesterol from the intestines into the bloodstream. Zetia blocks this process.

Information on the side effects of Zetia is limited. Although it seems safe so far, clinical studies have been small and mostly short-term. Compared with people taking a placebo, those taking Zetia reported slightly more fatigue, gastrointestinal problems, infections such as sinusitis, and muscle and back pain. Although the low rate of side effects is reassuring, the true side effect profile won't be known until hundreds of thousands of people take the drug for several years.

Zetia reduces LDL levels about 20% alone; studies show that when combined with a statin, it lowers LDL another 15%–23%. Talk with your doctor about whether a combination strategy might be helpful for you, particularly if you have not responded dramatically to a statin alone. One combination medication is currently available that combines ezetimibe with a statin in a single pill (see below).

A cholesterol-lowering combination

Most available combination drugs for heart health treat high blood pressure (see "Combination medications"). In 2004, the FDA approved Vytorin, the first combination drug to control cholesterol. The drug was designed to offer a one-two punch: It combines simvastatin, which blocks production of cholesterol in the liver, and ezetimibe, which blocks absorption of cholesterol in the intestines. Although some studies have reported that Vytorin lowers cholesterol more than a statin alone, it remains unclear whether this medication, or even the combination strategy, will prevent more heart attacks and deaths than other treatment approaches.

Selective estrogen receptor modulators (SERMs)

Sometimes called "designer estrogens," selective estrogen receptor modulators (SERMs) block the effects of estrogen in some parts of the body, such as the breasts, but not in others (which is why they are called selective). One of these drugs, raloxifene (Evista), decreases levels of both total and LDL cholesterol, but does not increase HDL. However, the net effect on overall heart disease risk is unknown at this point.

Last updated:	May 03, 2007